In Response to RFA DK-08-011, Vanderbilt University, a TrialNet Major Affiliate since 2006, proposes to become a Clinical Center. William E. Russell, MD, TrialNet PI, will continue in that role. He is joined by James W. Thomas MD, as the Co-Investigator. Salient points of this proposal: (Vanderbilt became an active Major Affiliate (MA) of TrialNet in October, 2006, 28 months ago. With the modest resources of a MA we have recruited 591 subjects from 12 states into the Natural History Study; enrolled 2 subjects into the Oral Insulin Prevention Trial, and four subjects into the CTLA4-lg study. We are the only MA to engage in this intervention study. We have also recruited 433 subjects from 51 families into the T1 Diabetes Genetics Consortium, making us the leading T1DGC recruitment site internationally. (We document an strong institutional support for the goals and activities of TrialNet, including: a commitment by Dr. Jonathan Gitlin, Chair of Pediatrics to fund an additional 1.0 FTE of TrialNet study coordinator; the strong endorsement of Dr. Gordon Bernard Director of the CTSA offering the full services of the CRCs; and a commitment by Dr. Alvin Powers to expand dedicated space in the VEDC, provide 0.5 FTE of administrative support, and the full resources of the Vanderbilt Diabetes Center for TrialNet. (The investigators are highly experienced and well-suited to carrying out the aims of a TrialNet Clinical Center. With the input of a Vanderbilt TrialNet Scientific Advisory Committee, they propose a diabetes intervention trial Combined inflammatory blockade and oral tolerance for intervention in T1D. (New strategies and alliances are proposed to facilitate recruitment to TrialNet studies at the level of a Clinical Center. Among them are partnerships with the TN Department of Healt and other instutitions with a far reach into our region. A Remote Recruitment Program and possible Mibile Clinical Research Unit are proposed to take our screening activities far beyond middle TN. (A TrialNet Community Advisory Board has been established to secure input regarding screening and outreach strategies from a variety of diabetes stakeholders in our region.